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Why anaesthetics can make the pain worse

By Alison Motluk

When you undergo surgery, you expect general anaesthetic to take the pain away, not make it worse. But new research suggests that many commonly used anaesthetics may worsen post-operative soreness and inflammation by activating peripheral pain pathways.

Gerard Ahern at Georgetown University in Washington DC and his colleagues have now figured out how this happens. Their work could help doctors choose the least painful anaesthetic for different medical procedures.

General anaesthetics work by depressing the central nervous system and inducing temporary unconsciousness. Some general anaesthetics also cause pain, however. For instance, Propofol often causes a burning sensation at the injection site, while isoflurane can seriously irritate the respiratory tract.

The researchers tested the effects of various anaesthetics on different receptors found on sensory neurons and found that ones that caused pain activated a receptor called TRPA1.

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To confirm whether this was the channel mediating pain, the researchers injected different anaesthetics into the noses of mice genetically engineered to lack the receptor. These mice did not experience pain whereas ordinary mice did.

Inflamed ears

The researchers also wanted to see if some anaesthetics contributed to inflammation. When an inflammatory agent was applied to the ears of mice anaesthetised with isoflurane, the mice experienced significantly more swelling than mice that received another kind of anaesthetic.

Since general anaesthesia use almost always coincides with surgical tissue damage, the researchers say the wrong choice of anaesthetic could lead to extra pain and inflammation. Surgeons might consider giving more thought to which anaesthesia drugs they select, says Ahern.

Some newer, more expensive agents, such as sevoflurane, do not activate the TRPA1 receptor, and so should not contribute to pain and inflammation. Alternatively, pre-emptive inhibitors that blunt the extra pain could be developed and administered alongside the more pungent general anaesthetics, he suggests.